title: A selective role for dopamine D₄ receptors in modulating reward expectancy in a rodent slot machine task.
abstract: BACKGROUND
  Cognitive distortions regarding gambling outcomes confer vulnerability to pathological gambling. Using a rat slot machine task (rSMT), we previously demonstrated that the nonspecific D₂ agonist quinpirole enhances erroneous expectations of reward on near-miss trials, suggesting a pivotal role for the D₂ receptor family in mediating the near-miss effect. Identifying which receptor subtype is involved could facilitate treatment development for compulsive slot machine play.
  
  
  METHODS
  Thirty-two male Long Evans rats learned the rSMT. Three flashing lights could be set to on or off. A win was signaled if all three lights were set to on, whereas any other light pattern indicated a loss. Rats then chose between responding on the collect lever, which delivered 10 sugar pellets on win trials but a 10-second time penalty on loss trials, or to start a new trial instead. Performance was assessed following systemic administration of selective D₂, D₃, and D₄ receptor ligands.
  
  
  RESULTS
  The selective D₂ antagonist L-741,626, the D₃ antagonist SB-277011-A, and the D₃ agonist PD128,907 had no effect. In contrast, the selective D₄ agonist PD168077 partially mimicked quinpirole's effects, increasing erroneous collect responses on nonwin trials, whereas the D₄ antagonist L-745,870 improved the error rate. L-745,870 was also the only antagonist that could attenuate the deleterious effects of quinpirole.
  
  
  CONCLUSIONS
  The dopamine D₄ receptor is critically involved in signaling reward expectancy in the rSMT. The ability of L-745,870 to reduce the classification of losses as wins suggests that D₄ antagonists could be effective in treating problematic slot machine play.
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver. Electronic address: pcocker@psych.ubc.ca.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cocker
authors.affiliation: Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, Ontario, Canada; Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Pharmacology, Family and Community Medicine, and Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Department of Psychiatry, Bangor University, Bangor, United Kingdom.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Rogers
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver.
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Winstanley
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012201:Reward; D012309:Risk-Taking
chemical_list: C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D001549:Benzamides; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D050638:Receptors, Dopamine D4
keywords: Anterior cingulate; L-745,870; gambling; incentive salience; near-miss; quinpirole